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Expert Critique

FROM THE ASCO Reading Room

Krista Gonzales, MD Endocrinologist Leon Medical Centers

Brittle Diabetes, a term coined in the 1940s, is considered an antiquated term. As knowledge and technology have advanced, clinicians now recognize that widely variable fluctuations in glucose levels ultimately have an underlying cause. Although, there are still some cases that are more challenging and difficult to manage. As noted, prognosis is poor in patients with 鈥渂rittle diabetes.鈥� They tend to have lower QOL scores, more microvascular complications, and shortened life expectancies. Three forms have been described: recurrent diabetic ketoacidosis, predominant hypoglycemic forms, and mixed instability. The assessment of brittle diabetes requires quantification of the variability of blood glucose levels. Multiple measuring systems are available to quantify instability, including Mean of Daily Differences (MODD), Mean Amplitude of the largest Glycemic Excursions (MAGE), and Lability Index (LI). Currently, healthcare providers prefer terms such as labile diabetes, glucose variability, or uncontrolled diabetes over the term brittle diabetes.

Contributing factors can take investigational work on the provider鈥檚 part and often more time than the typical 20-minute appointment. Moreover, the cause can vary from patient to patient. Common etiologies include: inconsistencies in diet and physical activity, psychosocial, medication adherence, proper administration, overcorrection of hypo/hyperglycemia, adherence to self glucose monitoring, asymptomatic hypoglycemia, and other conditions such as depression, alcohol abuse, renal disease, and gastroparesis. Uncovering and treating the cause is the key. Asymptomatic hypoglycemia, a common cause of high glucose variability, can cause resultant hyperglycemia from exaggerated overcorrection upon detection of hypoglycemia. One solution to this paradox is avoidance of hypoglycemia by allowing a higher overall baseline glucose for a set time. This can restore the patient鈥檚 ability to perceive hypoglycemia.

Technological advancement, insulin pumps and CGMs, provide closer monitoring and ultimately assist in the detection of some underlying problems. However, a heightened level of awareness and increased investigational skills by both patients and clinicians is needed for improved glycemic control.

Full Critique

The diagnosis of "brittle diabetes" appears to be a relic, harkening back to a time before technology made it possible to pinpoint specific factors driving the variation in management of the disease. However, the underlying circumstances that earned that appellation -- chronically unstable diabetes, usually type 1 and usually in a child or young adult, for which there is no apparent explanation for glucose fluctuations -- are certainly real.

"Brittle diabetes has now become unconventional," said , a clinical dietitian and certified diabetes educator. "People used to think diabetes had its own mind, but now we know a lot more. It's just [a matter of] getting the right tools, the right education, the right treatment."

The term "brittle diabetes" was first coined in the 1940s. it affects about 3/1000 insulin-dependent diabetic patients and can disproportionately affect young women. In the decades since, as knowledge and technology have advanced, more and more clinicians have come to believe that, while some diabetes cases do pose unusual challenges, fluctuations typically have an underlying cause, such as inconsistencies in diet, medication compliance or other things. A the main causes of "brittleness" as malabsorption, certain drugs, including alcohol and antipsychotics, defective insulin absorption or degradation, defective hyperglycemic hormones, especially, and delayed gastric emptying. However, the study also noted that "psychosocial factors are very important and factitious brittleness may lead to a self-perpetuating condition." A of the topic found that "indications of psychological disturbance in the children and their parents" accounted for 44% of variance in blood glucose control.

"Patients and their providers use it as a fall back or an excuse to stop looking for answers," said , a diabetes educator and the owner and clinical director of Integrated Diabetes Services, based in Pennsylvania. "They think there's nothing they can do, but that's not the case."

Depending on the circumstances, clinicians and educators now prefer terms such as labile diabetes, glucose variability or, simply, uncontrolled diabetes.

No Matter the Name - Focus on the Cause

Either way, debates over terminology may occlude the real issue -- how best to address the fluctuations.

"'Brittle diabetes' reflects two possibilities: poor diabetes management in patients who could do much better with a bit more effort ... or serious and uncontrolled fluctuations in blood glucose concentrations in specific diabetes types like type 1 diabetes or type 3 pancreatogenic diabetes," said , a diabetologist and researcher with General Hospital Slovenj Gradec in Slovenia.

In the subset of cases where diabetes is not optimally controlled, experts have found a common pattern that is relatively easy to address.

"The most frequent cause [of glucose fluctuation] nowadays is the presence of asymptomatic hypoglycemia that leads to a hyperglycemic rebound," said , MD, a diabetologist with Albert Einstein Hospital in São Paulo, Brazil. "Upon detection, the patient corrects glucose levels with exaggeration, causing a new hypoglycemic event. The easiest way to deal with the problem is to avoid hypoglycemic events for at least three weeks ... After a period without hypoglycemia, the patient recovers the capacity to perceive hypoglycemia and to avoid its occurrence."

A published in the Journal of Diabetes Research posited, among other things, that many cases of glucose variability had psychological roots.

"There are many new, high-tech devices to measure blood glucose -- almost continuously. However, none of this technology addresses the root of the problem in 'brittle diabetes,' since all of these medical aids require rational minds operating them," said lead study author of the Center of Child and Adolescent Medicine at Justus Liebig University in Germany. "The dissolution of the parent-child relationship during puberty and adolescence may trigger psychological states in which some adolescents suffering from type 1 diabetes may lose rational control over their blood sugar management."

Gunther and others support, as Gunther puts it, "psychosomatic interventions in addition to evidence-based individually adjusted medical treatment of the diabetes, adequate and normalized schooling of the minors and their close relatives or care-givers, and close monitoring of treatment success through specific parameters."

Solutions for Better Glycemic Control

The idea of closer monitoring is at the heart of most ways around "brittle diabetes." Newer but relatively widely available technologies like insulin pumps and continuous glucose monitoring are at the heart of such efforts.

Perhaps more importantly than the actual tools, however, is the fact that patients and clinicians must be prepared to gather and sort through large amounts of information, in order to gather meaningful and actionable data and patterns, experts said.

"Firstly, a detailed analysis is required to try to explain the blood sugar swings," said Makuc. "What are the patients' eating habits, physical activity? Does he take his therapy? Does he apply it correctly (correct time, body place, etc)? Does he have the optimal therapy (optimal insulin selection, correct dosing)? Does he have other conditions (depression, drinking problems, etc.)? How does he measure his blood sugar levels? Are the measuring strips within the shelf life? For detailed analysis we can use technological support (e.g. CGMS) and this almost always reveals what's to blame."

Obvious culprits like dietary changes may be one area to explore, but there are others, and relatively common tools can help tease out the areas.

"There is software that can break out data by day of the week," Scheiner said. "Let's say Tuesday and Thursday there were big spikes. You see there were stressful meetings or someone was going out to lunch those days ... There's an almost unlimited number of variables, but we can always figure it out."